Chorionic villous biopsy (CVB) has been introduced as a method of first trimester prenatal diagnosis. The technique of biopsy has become partly standardized and the use of the method is quickly expanding in Europe and North America. Valid information about safety and accuracy of the procedure is very limited at present and is necessary to responsibly guide and control the growth of CVB to the benefit of pregnant women and their developing babies. This project, as part of a cooperative effort with other medical centers, aims to provide that necessary information. From a population of 900 women per year (75 per month who have increased risk of fetal disease and who request prenatal diagnosis at our medical center, we shall attempt to identify 20 per month for 2-1/2 years who will accept randomization of their diagnostic procedure between CVB and amniocentesis. These women, through the cooperation of their obstetricians, will be identified by the eighth week of pregnancy and followed for the remainder of pregnancy with sonographic imaging, clinical obstetric data, and examination of newborns or other products of conception. We shall utilize the clinical and diagnostic laboratory services at our medical center to give standardized and complete information at the time of the diagnostic procedure and including the chromosomal, biochemical, and molecular genetic definition of the fetus. The babies will be examined at the time of birth and we propose a questionnaire with selected examinations to follow the children to age one. Women who decline randomization between CVB and amniocentesis and who elect CVB will be followed in an identical manner as those who are randomized. We expect that the experience of the cooperating centers, using a standard protocol, will permit accurate definition for CVB of miscarriage risks (for both CVB patients and a control population), and of other possible risks to the pregnant woman and her developing baby. The accuracy of diagnosies based on chorionic villi will also be defined and both the safety and accuracy of CVB will be able to be contrasted with those of amniocentesis.